U. professor helps identify antibody as key to fighting hepatitis C

Broadly neutralizing antibodies, arecently discovered type of antibody, may be the key to helping combat the hepatitis C virus, according to a recent study conducted by University researchers doneon laboratory mice with humanized livers.

A humanized liver is a mouse liver that has had human liver cells inserted into it. Hepatitis C viruses can only be tested on mice with humanized livers because the virus only infects humans and primates, who are not allowed to be test subjects.

The researchers worked with two groups of mice, one treated with normal antibodies and one with thebroadly neutralizing antibodies discovered by co-author Mansun Law and other researchers at the ScrippsResearch Institute. While the hepatitis C virus is very evasive and hard to treat because of its ability tomutate and change,the team found that the virus could not get around the broadly neutralizing antibodies by mutating.

“What we were looking for was, 'Were there any mutations in the HCV that allowed the HCV toessentially escape from basically being neutralized by the antibodies themselves?' and what we found was thatthere weren’t any,” Benjamin Winer GSsaid.

Molecular biology assistant professor Alex Ploss, a co-author of the study, explained that the treatment of hepatitis C virus is important because of the overwhelming number of people it infects. Approximately 150 million people worldwidesuffer from chronic hepatitis C virus infection, with an estimated three to four million in the US.Chronic infectionleads to an ongoing immune response where the virus continually mutates to hide from theimmune system.

“This can go on for decades,” Ploss said.

Law described the virus as a “silentkiller” because so many people are infected with the virus and do not know unless they take ablood test. Hepatitis C can lead to liver damage, cirrhosis and cancer. According to the World HealthOrganization, it is caused by “unsafe injection practices; inadequate sterilization of medical equipment insome health-care settings; and unscreened blood and blood products.”

Research specialist Sherif Gerges, who worked on the study, explained that the antibodies worked because thevirus's envelope, its outer coat used to enter other cells, does not mutate as much as the rest of thevirus.

“There are regions within this coat that are targets or potential targets for these antibodies,”Gerges said.

The team found that after sequencing the virus and the regions of the envelope, there were no adaptivemutations within the 12 mice studied, meaning that the antibodies contained the virus.

Andrea Cox, associate professor of medicine and oncology at Johns Hopkins University, also pointed to the importance of preventing hepatitis C virus.

“It is very interesting to contemplate potentially successful methods for inducing immuneresponses that protect against hepatitis C viral infection,” Cox said.

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Current therapies that are able to remove the virus are very expensive, do not prevent the virus fromcoming back and leave behind damage in the liver, Ploss said. While it is unknown if these results can bemimicked in human beings, and human trials are very far off, these results could point to a new strategy to prevent hepatitis C.

“This is a promising potentialstrategy for developing protection from hepatitis C virus infection that I think is worth further exploration,” Cox said.

The study was published on Sept. 17 in Science Translational Medicine.